Subscribe to RSS
Risk factors and long-term course of gastroesophageal reflux disease after peroral endoscopic myotomy: A large-scale multicenter cohort study in JapanSupported by: JGA Clinical Research Grants, Multicenter Research Grant of The Japanese Foundation for Research and Promotion of Endoscopy 2021–1
Background Gastroesophageal reflux disease (GERD) and reflux esophagitis remain problems after peroral endoscopic myotomy (POEM). This study aimed to elucidate the risk factors and long-term course of reflux esophagitis and symptomatic GERD after POEM.
Methods This multicenter cohort study involved 14 high volume centers. Overall, 2905 patients with achalasia-related esophageal motility disorders treated with POEM were analyzed for reflux esophagitis, severe reflux esophagitis (Los Angeles classification C or D), and symptomatic GERD.
Results Reflux esophagitis was diagnosed in 1886 patients (64.9 %). Age ≥ 65 years (risk ratio [RR] 0.85), male sex (RR 1.11), posterior myotomy (RR 1.12), esophageal myotomy > 10 cm (RR 1.12), and gastric myotomy > 2 cm (RR 1.17) were independently associated with reflux esophagitis. Severe reflux esophagitis was diagnosed in 219 patients (7.5 %). Age ≥ 65 years (RR 1.72), previous treatments (RR 2.21), Eckardt score ≥ 7 (RR 0.68), sigmoid-type achalasia (RR 1.40), and esophageal myotomy > 10 cm (RR 1.59) were factors associated with severe reflux esophagitis. Proton pump inhibitors (PPIs) were more effective for reflux esophagitis at 5-year follow-up (P = 0.03) than after 1 year (P = 0.08). Symptomatic GERD was present in 458 patients (15.9 %). Symptom duration ≥ 10 years (RR 1.28), achalasia diagnosis (RR 0.68), integrated relaxation pressure ≥ 26 (RR 0.60), and posterior myotomy (RR 0.80) were associated with symptomatic GERD. The incidence of symptomatic GERD was lower at 5-year follow-up compared with that after 1 year (P = 0.04), particularly in PPI users (P < 0.001).
Conclusions The incidence of severe reflux esophagitis was low after POEM, but excessive myotomy for older patients with previous treatments should be avoided. Early phase symptomatic GERD is non-acid reflux dependent and the natural course is favorable, basically supporting conservative treatment.
Received: 16 September 2021
Accepted after revision: 03 January 2022
Article published online:
16 February 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
- 1 Inoue H, Minami H, Kobayashi Y. et al. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy 2010; 42: 265-271
- 2 Ponds FA, Fockens P, Lei A. et al. Effect of peroral endoscopic myotomy vs pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: a randomized clinical trial. JAMA 2019; 322: 134-144
- 3 Werner YB, Hakanson B, Martinek J. et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. NEJM 2019; 381: 2219-2229
- 4 Vaezi MF, Pandolfino JE, Yadlapati RH. et al. ACG Clinical Guidelines: Diagnosis and management of achalasia. Am J Gastroenterol 2020; 115: 1393-1411
- 5 Oude Nijhuis RAB, Zaninotto G, Roman S. et al. European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations. United European Gastroenterol J 2020; 8: 13-33
- 6 Inoue H, Shiwaku H, Iwakiri K. et al. Clinical practice guidelines for peroral endoscopic myotomy. Dig Endosc 2018; 30: 563-579
- 7 Schlottmann F, Luckett DJ, Fine J. et al. Laparoscopic Heller myotomy versus peroral endoscopic myotomy (POEM) for achalasia: a systematic review and meta-analysis. Ann Surg 2018; 267: 451-460
- 8 Familiari P, Greco S, Gigante G. et al. Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis. Dig Endosc 2016; 28: 33-41
- 9 Shiwaku H, Inoue H, Sato H. et al. Peroral endoscopic myotomy for achalasia: a prospective multicenter study in Japan. Gastrointest Endosc 2020; 91: 1037-1044 e2
- 10 Nabi Z, Ramchandani M, Kotla R. et al. Gastroesophageal reflux disease after peroral endoscopic myotomy is unpredictable, but responsive to proton pump inhibitor therapy: a large, single-center study. Endoscopy 2020; 52: 643-651
- 11 Kumbhari V, Familiari P, Bjerregaard NC. et al. Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study. Endoscopy 2017; 49: 634-642
- 12 Mota RCL, de Moura EGH, de Moura DTH. et al. Risk factors for gastroesophageal reflux after POEM for achalasia: a systematic review and meta-analysis. Surg Endosc 2021; 35: 383-397
- 13 Liu Z-Q, Li Q-L, Chen W-F. et al. The effect of prior treatment on clinical outcomes in patients with achalasia undergoing peroral endoscopic myotomy. Endoscopy 2019; 51: 307-316
- 14 Iwakiri K, Kinoshita Y, Habu Y. et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015. J Gastroenterol 2016; 51: 751-767
- 15 Sato H, Yokomichi H, Takahashi K. et al. Epidemiological analysis of achalasia in Japan using a large-scale claims database. J Gastroenterol 2019; 54: 621-627
- 16 Shrier I, Platt RW. Reducing bias through directed acyclic graphs. BMC Med Res Methodol 2008; 8: 70
- 17 Eckardt VF. Clinical presentations and complications of achalasia. Gastrointest Endosc Clin N Am 2001; 11: 281-292, vi
- 18 Kahrilas PJ, Bredenoord AJ, Fox M. et al. The Chicago Classification of esophageal motility disorders, v3. 0. Neurogastroenterol Motil 2015; 27: 160-174
- 19 Kuribayashi S, Iwakiri K, Kawada A. et al. Variant parameter values-as defined by the Chicago Criteria-produced by ManoScan and a new system with Unisensor catheter. Neurogastroenterol Motil 2015; 27: 188-194
- 20 Song BG, Min YW, Lee H. et al. Clinicomanometric factors associated with clinically relevant esophagogastric junction outflow obstruction from the Sandhill high-resolution manometry system. Neurogastroenterol Motil 2018; DOI: 10.1111/nmo.13221.
- 21 do Carmo GC, Jafari J, Sifrim D. et al. Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions. Neurogastroenterol Motil 2015; 27: 285-292
- 22 Japan Esophageal Society. Descriptive rules for achalasia of the esophagus, June 2012: 4th Edition. Esophagus 2017; 14: 275-289
- 23 Lundell LR, Dent J, Bennett JR. et al. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45: 172-180
- 24 Jones R, Junghard O, Dent J. et al. Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care. Aliment Pharmacol Ther 2009; 30: 1030-1038
- 25 Westreich D, Greenland S. The table 2 fallacy: Presenting and interpreting confounder and modifier coefficients. Am J Epidemiol 2013; 177: 292-298
- 26 Sato H, Sagara S, Suzuki K. et al. Assessments of histologic changes after peroral endoscopic myotomy. Gastrointest Endosc 2016; 84: 377-378
- 27 Ishimura N, Owada Y, Aimi M. et al. No increase in gastric acid secretion in healthy Japanese over the past two decades. J Gastroenterol 2015; 50: 844-852
- 28 Iijima K, Koike T, Abe Y. et al. Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men. J Gastroenterol 2015; 50: 853-861
- 29 Martino F, Perestrelo AR, Vinarský V. et al. Cellular mechanotransduction: from tension to function. Front Physiol 2018; 9: 824
- 30 Fujimoto K. Review article: prevalence and epidemiology of gastro-oesophageal reflux disease in Japan. Aliment Pharmacol Ther 2004; 20: 5-8
- 31 Furukawa N, Iwakiri R, Koyama T. et al. Proportion of reflux esophagitis in 6010 Japanese adults: prospective evaluation by endoscopy. J Gastroenterol 1999; 34: 441-444
- 32 Kamal F, Ismail MK, Khan MA. et al. Efficacy and safety of peroral endoscopic myotomy in the management of recurrent achalasia after failed Heller myotomy: a systematic review and meta-analysis. Ann Gastroenterol Hepatol 2021; 34: 155-163
- 33 Ponds FA, Oors JM, Smout AJPM. et al. Reflux symptoms and oesophageal acidification in treated achalasia patients are often not reflux related. Gut 2021; 70: 30-39
- 34 Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108: 308-328; quiz 329
- 35 Dirac MA, Safiri S, Tsoi D. et al. The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020; 5: 561-581